Quantum Mechanics Study on Hydrophilic and Hydrophobic Interactions in the Trivaline–Water System

Abstract

With the aim to elucidate hydrophobic effects in the unfolded state of peptides, DFT-M062X computations on the ValH· nHO ( n up to 22) clusters have been accomplished. As far as the main chain is concerned, four conformers with β-strand and/or polyproline type II conformations, PPII (indicated as β-β, β-PPII, PPII-β, and PPII-PPII), have been found by changing the ϕ and ψ angles. For bare peptide, the side chain (isopropyl) of each residue can independently take on three different orientations with negligible effects on energetics. The great isopropyl spatial separations in β-β and β-PPII conformers allow for the construction of synergic and extensive water-water and water-peptide H-bonding in the minimal hydration ValH·22HO models without significant steric encumbrance. Conversely, due to the proximity of the isopropyl of the central residue with the other two, some restrictions in the water shell construction around the peptide become evident for the PPII-PPII conformer and the number of energetically accessible structures decreases. This is indicative of correlated motion involving isopropyls and backbone mediated by water molecules, the origin of the nearest neighbor effects. Comparing the thermodynamic data of AlaH·22HO and ValH·22HO, what emerges is that both hydration enthalpy and entropy drive the β-strand stability of the latter.

The water molecule arrangement over the side chain of some aliphatic amino acids: A quantum chemical and bottom‐up investigation

“…Water molecule and hydrocarbon interactions were studied previously for the H 2 O·CH 4 prototype . A shallow minimum with a stabilization energy of −0.6 kcal mol −1 and a H 2 O⋯CH 4 distance of 3.4 Å was found at the present M06‐2X/6‐31+G*/PCM computational level.…”

“…For valine, Roberts et al reported a predominance of rotamer II in all ionized states and differences in populations are more pronounced than those found in α‐aminobutyric acid. The bulky isopropyl side chain poses important restrictions in internal amino acid movements as already proposed for the trivaline …”

“…Hydrocarbon‐water interactions are weakly attractive and for the H 2 O·CH 4 prototype a stabilization energy of −0.6 kcal mol −1 was found . The water‐water hydrogen bonds are much more attractive (about −5 kcal mol −1 ), thus when a hydrophobe is embedded into water it changes the structure of interfacial water and a cavity is formed .…”

“…Recently, we reported a protocol to evaluate hydration effects on molecular properties by means of full quantum mechanics methods for atomic interactions along with a bottom‐up approach for the water shell construction around di‐ and tripeptides . Those investigations provided useful information on the intimate solute‐water contacts and in particular, it was shown that hydrophilic interactions among water molecules and peptide polar groups were very important for molecular structures and thermodynamic function predictions.…”

“…Those investigations provided useful information on the intimate solute‐water contacts and in particular, it was shown that hydrophilic interactions among water molecules and peptide polar groups were very important for molecular structures and thermodynamic function predictions. In those studies the hydration of the nonpolar side chain was partially taken into account; nevertheless, it was shown that highly hydrophobic side chains, as in the case of Val 3 H + , significantly perturb water‐hydrophilic group interaction …”